Enantioselective Rh-catalyzed hydrogenation of vinyl carboxylates with monodentate phosphite ligands

Article abstract of DOI:10.1021/ol035076p

(Matrix presented) Alkyl-substituted vinylcarboxylates, which normally show poor enantioselectivity in Rh-catalyzed hydrogenation with traditional chiral diphosphines, undergo highly enantioselective reactions with BINOL- and carbohydrate-based monophosph

Full text of DOI:10.1021/ol035076p

ORGANIC
LETTERS
2
003
Vol. 5, No. 17
099-3101
Enantioselective Rh-Catalyzed
Hydrogenation of Vinyl Carboxylates
with Monodentate Phosphite Ligands
3
†
Manfred T. Reetz,* Lukas J. Goossen,* Andreas Meiswinkel, Jens Paetzold, and
Jakob Feldthusen Jensen
Max-Planck-Institut f u¨ r Kohlenforschung, Kaiser-Wilhelm-Platz 1,
D-45470 M u¨ lheim/Ruhr, Germany
reetz@mpi-muelheim.mpg.de; goossen@mpi-muelheim.mpg.de
Received June 13, 2003
ABSTRACT
Alkyl-substituted vinylcarboxylates, which normally show poor enantioselectivity in Rh-catalyzed hydrogenation with traditional chiral
diphosphines, undergo highly enantioselective reactions with BINOL- and carbohydrate-based monophosphite ligands.
The asymmetric Rh-catalyzed hydrogenation of enol esters
with formation of chiral esters constitutes an alternative to
the enantioselective reduction of the corresponding prochiral
ketones. Moreover, enol esters are not only accessible from
ketones, but also from alkynes by metal-catalyzed reaction
with carboxylic acids. A particularly mild and efficient
version of the latter reaction 1 + 2 f 3, using commercially
catalyzed asymmetric olefin hydrogenation using cheap and
readily accessible BINOL-derived monodentate phosphites
(Scheme 1, bottom). Other groups have already reported
3
efficient ligand systems for the hydrogenation of enol
acetates, although high enantioselectivities (ee > 90%) were
restricted to substrates bearing aryl, vinyl, or trifluoromethyl
1
4
groups at the olefinic function. In the case of alkyl residues,
available [(p-cymene)RuCl
2
]
2 3
PR , was recently reported by
enantioselectivity is consistently mediocre (e.g., 64% ee in
one of us (Scheme 1, top).2
the case of the hydrogenation of 3 with R ) n-C
7
H15 and R′
5
)
CH ). In the present study we focus on this problem. To
3
tune the reaction, we envisioned the variation of the nature
of the R′ group in 3 as well as optimization of the modular
chiral monophosphite 6 employed as the ligand in the Rh
Scheme 1
(
1) (a) Rotem, M.; Shvo, Y. Organometallics 1983, 2, 1689-1691. (b)
Mitsudo, T.; Hori, Y.; Watanabe, Y. J. Org. Chem. 1985, 50, 1566-1568.
c) Mitsudo, T.; Hori, Y.; Yamakawa, Y.; Watanabe, Y. J. Org. Chem.
(
1
987, 52, 2230-2239. (d) Doucet, H.; H o¨ fer, J.; Bruneau, C.; Dixneuf, P.
H. J. Chem. Soc., Chem. Commun. 1993, 850-851. (e) Doucet, H.; Martin-
Vaca, B.; Bruneau, C.; Dixneuf, P. H. J. Org. Chem. 1995, 60, 7247-
7
255. (f) Doucet, H.; Derrien, N.; Kabouche, Z.; Bruneau, C.; Dixneuf, P.
H. J. Organomet. Chem. 1997, 551, 151-157. (g) Bruneau, C.; Neveux-
Duflos, M.; Dixneuf, P. H. Green Chem. 1999, 1, 183-185.
(2) Goossen, L. J.; Paetzold, J.; Koley, D. Chem. Commun. (Cambridge,
U.K.) 2003, 706-707.
The goal of the present study was to test compounds of
the type 3 in our previously described method of Rh-
(3) (a) Reetz, M. T.; Mehler, G. Angew. Chem. 2000, 112, 4047-4049;
Angew. Chem., Int. Ed. 2000, 39, 3889-3890. (b) Reetz, M. T.; Sell, T.;
Meiswinkel, A.; Mehler, G. Angew. Chem. 2003, 115, 814-817; Angew.
Chem., Int. Ed. 2003, 42, 790-793. (c) Chen, W.; Xiao, J. Tetrahedron
Lett. 2001, 42, 2897-2899. (d) Komarov, I. V.; B o¨ rner, A. Angew. Chem.
2001, 113, 1237-1240; Angew. Chem., Int. Ed. 2001, 40, 1197-1200.
†
Dedicated to Professor Dr. Helmut Schwarz on the occasion of his
6
0th birthday.
1
0.1021/ol035076p CCC: $25.00 © 2003 American Chemical Society
Published on Web 07/25/2003

catalyst (Scheme 2). Specifically, we use chiral carbohydrate-
based alcohols in the synthesis of the phosphites.
Table 1. Rh-catalyzed Hydrogenation of 3aa
conversion,b
ee, % (config
of product)b
entry
ligand
%
Scheme 2
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6a (R)
6b (R)
6c (R)
6d (R)
6e (R)
6f (S)
6g (R)
6h (R)
7a
7b
7c
7d
7e
100
40
21.8 (S)
25.2 (S)
31.6 (S)
20.8 (S)
39.4 (S)
43.8 (R)
64.8 (S)
37.4 (S)
86.4 (S)
12.8 (R)
39.2 (S)
23.0 (S)
68.0 (S)
17.2 (R)
51.2 (S)
4.2 (R)
100
100
100
100
100
100
100
100
100
82
1
1
1
1
1
1
100
100
100
100
7f
7g
7h
In exploratory experiments the benzoate 3a was hydro-
genated by using a selected number of previously described
phosphites 6a-h in addition to several new carbohydrate-
based derivatives 7a-h. The synthesis of the latter ligands
proceeded without any problems in analogy to the reaction
16
a
Catalyst prepared in situ from Rh(cod)2BF4 and 2 equiv of ligand 6 or
7 in CH2Cl2; substrate:catalyst ) 200:1; 60 bar H2; 30 °C; 20 h.
Determined by GC.
b
3
shown in Scheme 2. The carbohydrate alcohols are all
enantioselectivity, with the exception of the neopentyl-
derived ligand 6g (entry 7). The ee value of 64.8% is
respectable for this type of transformation (ee upon using
BINAP: 13.6%), although it is of no practical value. In the
case of the carbohydrate-derived ligands, a remarkable trend
evolves. In all instances a pronounced difference in the
matched versus mismatched combinations becomes apparent
commercially available. In all cases the cationic rhodium
catalyst was prepared in situ by treating Rh(cod) BF (cod
2 4
)
6
1,5-cyclooctadiene) with 2 equiv of a monodentate ligand
or 7, in full analogy to our previous studies.3
(entries 9-16), a phenomenon that has not been previously
observed with other substrates and other chiral phosphites
3
containing two sources of chirality. The best case involves
the use of phosphite 7a prepared from R-BINOL and a
glucose derivative, resulting in an ee value of 86.4% (entry
9
).
We then studied the effect of the nature of the acid 2 used
in the synthesis of 3, although not all of the phosphite ligands
were tested. Table 2 shows that this type of influence is rather
Table 2. Rh-Catalyzed Hydrogenation of 3b-ea
conversion,b
%
ee, % (config
of product)b
entry
substrate
ligand
1
2
3
4
5
6
7
8
9
3b
3b
3c
7a
7b
7a
7b
7a
7b
7a
7a
7a
7b
100
93
100
88
100
44
100
100
100
76
73.6 (S)
31.6 (R)
74.4 (S)
6.2 (R)
41.6 (S)
10.4 (S)
90.4 (S)
94.0 (S)
93.0 (S)
22.0 (R)
The results of these experiments are summarized in Table
. Most of the simple phosphites lead to low degrees of
1
3c
(
4) (a) Ohkuma, T.; Kitamura, M.; Noyori, R. In Catalytic Asymmetric
Synthesis; Ojima, I., Ed.; Wiley-VCH: Weinheim, Germany, 2000; pp
-110. (b) Tang, W.; Liu, D.; Zhang, X. Org. Lett. 2003, 5, 205-207. (c)
Wu, S.; Wang, W.; Tang, W.; Lin, M.; Zhang, X. Org. Lett. 2002, 4, 4495-
497. (d) Chi, Y.; Zhang, X. Tetrahedron Lett. 2002, 43, 4849-4852. (e)
3d
3d
3e
3ec
3ec,d
3e
1
4
Li, W.; Zhang, Z.; Xiao, D.; Zhang, X. J. Org. Chem. 2000, 65, 3489-
496. (f) Jiang, Q.; Xiao, D.; Zhang, Z.; Cao, P.; Zhang, X. Angew. Chem.
999, 111, 578-580; Angew. Chem., Int. Ed. 1999, 38, 516-518. (g) Ohta,
T.; Miyake, T.; Seido, N.; Kumobayashi, H.; Takaya, H. J. Org. Chem.
3
1
10
a
1
995, 60, 357-363. (h) Le Gendre, P.; Braun, T.; Bruneau, C.; Dixneuf,
The same conditions were used as already described in Table 1.
b
Determined by GC. c This reaction was carried out at -20 °C. The
d
P. H. J. Org. Chem. 1996, 61, 8453-8455. (i) Burk, M. J. J. Am. Chem.
Soc. 1991, 113, 8518-1519.
substrate:catalyst ratio was increased to 500:1.
(5) Boaz, N. W. Tetrahedron Lett. 1998, 39, 5505-5508.
3100
Org. Lett., Vol. 5, No. 17, 2003

pronounced, the highest enantioselectivity (ee ) 90.4%)
resulting from the use of substrate 3e derived from furan-
Table 3. Rh-catalyzed Hydrogenation of 3f-ha
2-carboxylic acid in combination with ligand 7a (entry 7).
conversion,b
ee, % (config
of product)b
Upon reducing the temperature to -20 °C, enantioselectivity
increases to ee ) 94.0%. Hydrogenation of 2-hexanone is
not a better alternative since the most effective ligand (Penn
entry
substrate
ligand
%
1
2
3
4
5
6
7
8
3f
3f
3g
3g
3h
3h d
7a
7b
7a
7b
7a
7a
7a
7b
100
79
80.4 (S)
10.8 (R)
71.6 (S)c
4.8 (R)c
83.6 (S)
88.4 (S)
88.6 (S)
34.2 (R)
6
PHOS) leads to an ee value of only 75%. Moreover, the
7
100
100
100
100
99
analogous BINOL-derived phosphoramidite is also not well
suited in these cases (<10% conversion of 3a under the
standard reaction conditions as defined in Table 1).
The beneficial effect of using furan-2-carboxylic acid also
arises when employing ligands other than 7. An example
concerns the hydrogenation of 3e with ligand 6d, which
results in an ee value of 41.2% (S). In contrast, the
hydrogenation of the corresponding benzoate 3a employing
the same ligand leads to an enantioselectivity of only 20.8%
3h d,e
3h
66
a
The same conditions were used as already described in Table 1.
b Determined by GC. c Configurational assignment based on analogy. d This
reaction was carried out at -20 °C. The substrate: catalyst ratio was
increased to 500:1.
e
(Table 1, entry 4).
Upon turning to the even more difficult substrates 3f-h
monophosphite ligand the rhodium-catalyzed hydrogenation
of particularly difficult vinyl carboxylates 3 can be performed
with high enantioselectivity. Since the vinyl carboxylates are
accessible not only from ketones, but also by the Ru-
catalyzed addition of carboxylic acids to alkynes, interesting
synthetic possibilities arise.
having an ethyl substituent at the olefinic function, a similar
trend was observed (Table 3). Again, ligand 7a turned out
to be most effective, specifically in the hydrogenation of the
furanyl substrate 3h, leading to ee ) 83.6% at room
temperature and 88.6% at -20 °C (entries 6-8). Currently
it is difficult to pinpoint the reason for enhanced enantiose-
lectivity when using substrates derived from furan-2-car-
boxylic acid.
Acknowledgment. We thank the Fonds der Chemischen
In summary, we have demonstrated that by tuning the
nature of the carboxylate as well as varying the chiral
Industrie for generous support.
(
6) Jiang, Q.; Xiao, D.; Cao, P.; Zhang, X. Angew. Chem. 1998, 110,
203-1207; Angew. Chem., Int. Ed. 1998, 37, 1100-1103.
7) (a) van den Berg, M.; Minnaard, A. J.; Schudde, E. P.; van Esch, J.;
de Vries, A. H. M.; de Vries, J. G.; Feringa, B. L. J. Am. Chem. Soc. 2000,
Supporting Information Available: Spectral data of all
new ligands as well as a typical procedure for hydrogenation.
This material is available free of charge via the Internet at
http://pubs.acs.org.
1
(
1
22, 11539-11540. (b) Pe n˜ a, D.; Minnaard, A. J.; de Vries, J. G.; Feringa,
B. L. J. Am. Chem. Soc. 2002, 124, 14552-14553. (c) Pe n˜ a, D.; Minnaard,
A. J.; de Vries, A. H. M.; de Vries, J. G.; Feringa, B. L. Org. Lett. 2003,
5
, 475-478.
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3101